Thursday, June 21, 2018
UK Computer Science ... starting over?
This week the British Computer Society (BCS) writing from Roehampton University in South West London came very close to admitting that the introduction of Computer Science into English schools at GCSE and A level has been a bit of a disaster, cock up even.
A few years ago I was blogging for ComputerWorldUK and was one of the fiercest critics of the subject then called ICT and its apologist BECTA a government quango which effectively oversaw the digital revolution in schools at that time.
Long story short, BECTA was abolished, ICT given the chop ( last exams this year 2018 I believe) and Computing re-introduced ostensibly to re-create our pre-eminence in computing following a serious mocking of the current state of the nation by the then head of Google no less.
So enthused was I that I came out of teacher-retirement to teach the new GCSE and A levels in Computer Science. Maybe though I missed some early warning signs. At a educational show I was browsing a stall where the BCS was showcasing a child friendly drag and drop programming interface called Scratch. They ( the stall holders) were an odd bunch, very male very unfriendly and immune to dialogue ( ok criticism) or interest from a veteran MIndStorms block code user.
In other words very much what you might expect from a certain CompSci stereotype.
Anyway, what transpired was eye-opening
Firstly, CompSci at GCSE and A level is hard. I have taught Chemistry, Physics, Biology, ICT and Computing (c1998) at A level, GCSE and O level during my 38 years in the business. I and my students over the years would vote for Chemistry as the hardest; Physics as impossible without good maths; Biology “easiest but lots of it”; ICT as deeply trivial but useful in the workplace ( MS Office era) and 1990s Computing really quite easy. It’s a long list but it has been a long time albeit punctuated by 10yr back in industry post 2000.
But CompSci 2016-- trumps the lot, and the reason that CompSci is so hard? … the level of abstraction is very high.
This is a problem. Abstraction is expected to be part of the skill set of A level students but in all honesty some subjects have very little ( Biology and Geography spring to mind). CompSci has a lot. Consequently, only those students who can do this will pass in the subject let alone thrive.
Boys and girls are equally represented with regard to the ability to move from concrete to abstract work. So, from a subset of the school population ( the abstracters) will come the successful CompSci kids.
Boys though are over-represented in their love of computer hardware, computer games, and nefarious activities thus labelling the subject of CompSci as ‘male’. Many of the less successful CompSci students take the subject because of these drivers.
Now we have a double whammy, nay a treble whammy. A hard, ‘boys’ subject suitable for only those few with the best abstract handling abilities that does not deliver the League Table’s best grades. The BCS/Roehampton report here says just that in its very good summary paragraphs at beginning of the report. Worth a read.
Finally another whammy, this time it’s fatal. Poor uptake of the subject especially at A level means that it is too expensive to keep on a schools portfolio of offerings. Few schools can continue to subsidise a subject in the time of budget squeeze.
What’s to be done? Do we really want computer and programming skills in our upcoming generations?
Easy, drop Computer Science from GCSE and GCE. It belongs with the technical qualifications.
With technical qualifications the abstract can be balanced with meaningful applied skills, (something not achievable in traditional schools). More girls will be attracted just for the reason that an employable skill is an employable skill and they are as pragmatic as boys. Place this subject in large institutions ( 1000+) so that class sizes can be viable.
In conclusion, the re-introduction of Computing to schools has been botched by geeks who thought everyone was like them. By the way developing ‘Scratch’ was not a solution to accessing programming. It was a distracting dead end.
Tuesday, June 19, 2018
Mitochondrial morphology: aging and capacitance 2
Mitochondrial morphology is critical to understanding how energy demands are managed by cells. The key to understanding how this is regulated lays in an electrochemical capacitance model.
In a 2016 article from the Salk Institute, the importance of mitochondrial morphology was presented in its clearest form1. Essentially the team shows that mitochondria respond withregard to their size and shape, to AMPK* enzymes. These are in effect part of a signalling system that monitors cellular ATP levels.
A drop in ATP levels ( in response to exertion-demand or toxins/poisons ) causes the mitochondria population to shatter in as much as they don’t burst but divide into a collection of a much smaller spheroid population. This is in contrast to some of the large, sometimes exotic, reticulate and tubular confections that mitochondria can form.
Mitochondrial fusion and fission was the subject of the conjectures in the paper and such musings have been mine for many years. In my PhD thesis and observed many times subsequently sged, senescent cells often show ‘mega-mitochondria’ with spherical shape and few cristae. I have speculated on the meaning of this change at length in a previous blog2.
My conclusions were that this was a phenomenon driven by electrical capacitance and the maintenance of a critical threshold membrane potential.
The question then, in light of the research and evidence of a variation in morphology from Salk, is what is the significance of such an astonishing range of shape and size?
My thesis has always been that it concerns the electronic capacitance of a mitochondrion.
The free energy needed to drive the synthesis of ATP occurs at membrane potentials of 120+ mv. A mitochondrion with a large surface area, ie one with a great deal of inner membrane folding, must of course, meet the 120mv condition but will, by virtue of its larger internal surface area, have a greater capacitance.
This means, as in regular electronics, that it can store more energy than its counterparts with smaller capacitances. It is ‘easier’ to fully charge ( ie reach the critical threshold potential to produce ATP) an individual mitochondrion with a smaller capacitance than one with the higher values simply because it requires less charge. However TOTAL CAPACITANCE within a cell will the sum of the individual capacitances of the mitochondria.
It is also clear from ageing studies and the work illustrated by Salk that mitochondrial morphology (and hence capacitance) appears highly adaptive … but why?
In a very energetic high output cells ( say a bird or bat’s muscle cells ) you find many many very small tightly coupled ( ie low charge-leaking) mitochondria. In failing, senescent cells you see a few large swollen mitochondria with very little internal folding. In dividing cells, you can see an amazing network, a reticulum of fused and branching mitochondria wrapped around the nucleus undergoing division.
I think there are enough clues here to speculate on the role of mitochondrial morphology.
If I stick to the capacitance-charge model then it is possible to outline different scenarios.
Scenario 1: Small, high cristae level spheroids.
Each mitochondrion has a relatively small capacitance so will reach the ‘ATP charge level’ quickly. A population of small spheroids has a much larger external surface area, as delineated by the outer membrane, than do the equivalent super-reticulate structures. This ratio aids rapid transport of charge (supplied by food) to the mitochondrion. So although in time of high demand, individual mitochondria could discharge below their threshold easily, they can also be re-supplied very quickly.
This is consistent with finding of lots of small mitos as a result of high energy demands or even poisoning where resultant charge leakage across the membrane can be accommodated by ( using electronics analogy) drawing more current. High collective capacitance, high external surface area to maximise 'food' supply.
Scenario 2: Large reticulated structures.
A super-net of mitochondria, fully charged, stores a lot of energy within the inner-membrane folds but presents a relatively low external surface area in contrast with the spheroid extreme describe above.
In the extreme case of a dividing cell, the opportunity to ‘feed’ the mito-structures is lower than normal as the cell itself is otherwise engaged. However the free energy to power cell division (which requires a predictable and a modest amount of ATP) can be stored in the ‘giant capacitor’ that surrounds the nucleus. High capacitance and relatively low external surface.
Between the two extremes above must lay ‘normal’, ‘poisoned and senescent scenarios.
I would guess that in stable low ATP demand tissues mitochondrial fusion would be favoured, as if ‘stockpiling’ energy if the demand suddenly arose or if feeding was suspended for a while.. On the other hand in very high output tissues then small low capacitance mitochondria would favour fission.
In poisoned or senescent scenarios, charge-leakage across the inner mitochondrial membrane would demand an adaptive change to reduce capacitance. There are two ways of achieving this: small mitochondria with normal cristae or large mitochondria with fewer cristae.
My conjecture is that in a low-economy cell for example, a semi-senescent cell (in limbo like an underused muscle cell, parked and marked for death), a large medium capacity mitochondrion is superior to many smaller versions (with overall similar total capacity) because the risk of local depolarisation is reduced. That is, one small mitochondrion, although requiring less to charge it, a demand ( an energy draw) is much more likely to cause it to depolarise if it is already is leaking. This is critical because depolarisation could trigger the cascade leading to apoptosis.
The larger single mitochondrion is less likely to simply locally fail. It still might fail but not as in the case above have inevitable mini- failures. It is a case of all eggs in fewer baskets.
The Ageing Mitochondria Scenario
With age mitochondria lose the ability to divide (or fuse) and they leak more charge. This means that to meet the energy demands of a cell they cannot divide and regenerate in response to AMPK signalling even if it is still working. In order to maintain minimum capacitance to supply enough energy for the cell they need to enlarge. Hence the appearance of mega-mitochondria. After this response any failure in the supply side of 'food' or further leaking will spell the end.
*AMPK a collection of protein kinases activated by AMP (adenosine monophosphate) a marker for ATP levels ( adenosine triphosphate).
1) https://www.sciencedaily.com/releases/2016/01/160114152323.htm
2) https://www.blogger.com/blogger.g?blogID=3906287940044842441#editor/target=post;postID=5246291255183981633;onPublishedMenu=allposts;onClosedMenu=allposts;postNum=28;src=postname
In a 2016 article from the Salk Institute, the importance of mitochondrial morphology was presented in its clearest form1. Essentially the team shows that mitochondria respond withregard to their size and shape, to AMPK* enzymes. These are in effect part of a signalling system that monitors cellular ATP levels.
A drop in ATP levels ( in response to exertion-demand or toxins/poisons ) causes the mitochondria population to shatter in as much as they don’t burst but divide into a collection of a much smaller spheroid population. This is in contrast to some of the large, sometimes exotic, reticulate and tubular confections that mitochondria can form.
Mitochondrial fusion and fission was the subject of the conjectures in the paper and such musings have been mine for many years. In my PhD thesis and observed many times subsequently sged, senescent cells often show ‘mega-mitochondria’ with spherical shape and few cristae. I have speculated on the meaning of this change at length in a previous blog2.
My conclusions were that this was a phenomenon driven by electrical capacitance and the maintenance of a critical threshold membrane potential.
The question then, in light of the research and evidence of a variation in morphology from Salk, is what is the significance of such an astonishing range of shape and size?
My thesis has always been that it concerns the electronic capacitance of a mitochondrion.
The free energy needed to drive the synthesis of ATP occurs at membrane potentials of 120+ mv. A mitochondrion with a large surface area, ie one with a great deal of inner membrane folding, must of course, meet the 120mv condition but will, by virtue of its larger internal surface area, have a greater capacitance.
This means, as in regular electronics, that it can store more energy than its counterparts with smaller capacitances. It is ‘easier’ to fully charge ( ie reach the critical threshold potential to produce ATP) an individual mitochondrion with a smaller capacitance than one with the higher values simply because it requires less charge. However TOTAL CAPACITANCE within a cell will the sum of the individual capacitances of the mitochondria.
It is also clear from ageing studies and the work illustrated by Salk that mitochondrial morphology (and hence capacitance) appears highly adaptive … but why?
In a very energetic high output cells ( say a bird or bat’s muscle cells ) you find many many very small tightly coupled ( ie low charge-leaking) mitochondria. In failing, senescent cells you see a few large swollen mitochondria with very little internal folding. In dividing cells, you can see an amazing network, a reticulum of fused and branching mitochondria wrapped around the nucleus undergoing division.
I think there are enough clues here to speculate on the role of mitochondrial morphology.
If I stick to the capacitance-charge model then it is possible to outline different scenarios.
Scenario 1: Small, high cristae level spheroids.
Each mitochondrion has a relatively small capacitance so will reach the ‘ATP charge level’ quickly. A population of small spheroids has a much larger external surface area, as delineated by the outer membrane, than do the equivalent super-reticulate structures. This ratio aids rapid transport of charge (supplied by food) to the mitochondrion. So although in time of high demand, individual mitochondria could discharge below their threshold easily, they can also be re-supplied very quickly.
This is consistent with finding of lots of small mitos as a result of high energy demands or even poisoning where resultant charge leakage across the membrane can be accommodated by ( using electronics analogy) drawing more current. High collective capacitance, high external surface area to maximise 'food' supply.
Scenario 2: Large reticulated structures.
A super-net of mitochondria, fully charged, stores a lot of energy within the inner-membrane folds but presents a relatively low external surface area in contrast with the spheroid extreme describe above.
In the extreme case of a dividing cell, the opportunity to ‘feed’ the mito-structures is lower than normal as the cell itself is otherwise engaged. However the free energy to power cell division (which requires a predictable and a modest amount of ATP) can be stored in the ‘giant capacitor’ that surrounds the nucleus. High capacitance and relatively low external surface.
Between the two extremes above must lay ‘normal’, ‘poisoned and senescent scenarios.
I would guess that in stable low ATP demand tissues mitochondrial fusion would be favoured, as if ‘stockpiling’ energy if the demand suddenly arose or if feeding was suspended for a while.. On the other hand in very high output tissues then small low capacitance mitochondria would favour fission.
In poisoned or senescent scenarios, charge-leakage across the inner mitochondrial membrane would demand an adaptive change to reduce capacitance. There are two ways of achieving this: small mitochondria with normal cristae or large mitochondria with fewer cristae.
My conjecture is that in a low-economy cell for example, a semi-senescent cell (in limbo like an underused muscle cell, parked and marked for death), a large medium capacity mitochondrion is superior to many smaller versions (with overall similar total capacity) because the risk of local depolarisation is reduced. That is, one small mitochondrion, although requiring less to charge it, a demand ( an energy draw) is much more likely to cause it to depolarise if it is already is leaking. This is critical because depolarisation could trigger the cascade leading to apoptosis.
The larger single mitochondrion is less likely to simply locally fail. It still might fail but not as in the case above have inevitable mini- failures. It is a case of all eggs in fewer baskets.
The Ageing Mitochondria Scenario
With age mitochondria lose the ability to divide (or fuse) and they leak more charge. This means that to meet the energy demands of a cell they cannot divide and regenerate in response to AMPK signalling even if it is still working. In order to maintain minimum capacitance to supply enough energy for the cell they need to enlarge. Hence the appearance of mega-mitochondria. After this response any failure in the supply side of 'food' or further leaking will spell the end.
*AMPK a collection of protein kinases activated by AMP (adenosine monophosphate) a marker for ATP levels ( adenosine triphosphate).
1) https://www.sciencedaily.com/releases/2016/01/160114152323.htm
2) https://www.blogger.com/blogger.g?blogID=3906287940044842441#editor/target=post;postID=5246291255183981633;onPublishedMenu=allposts;onClosedMenu=allposts;postNum=28;src=postname
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